OBJECTIVE: To explore the effectiveness and safety of golimumab in the treatment of severe/refractory cardiovascular Behcet syndrome (BS). METHODS: We retrospectively analyzed the clinical data of nine patients diagnosed with severe/refractory cardiovascular BS and treated with golimumab from February 2018 to July 2020 in Peking Union Medical College Hospital. We analyzed levels of erythrocyte sedimentation rate (ESR) and high-sensitivity C-reactive protein (hsCRP), imaging findings, and the doses of glucocorticoids and immunosuppressive agents during the period of combined treatment with golimumab. RESULTS: Nine patients were enrolled, including 8 males and 1 female, with a mean age and median course of (37.0±8.6) years and 120 (60, 132) months, respectively. Seven patients presented with severe aortic regurgitation combined with other cardiovascular involvement secondary to BS. Two patients presented with large vessel involvement, including multiple aneurysms and vein thrombosis. Prior to golimumab treatment, seven patients were treated with glucocorticoids and multiple immunosuppres-sants [with a median number of 3 (1, 3) types] while still experienced disease progression or elevated inflammation biomarkers during postoperative period. Eight patients with disease progression, uncontrolled inflammation and history of severe postoperative complications required effective and fast control of inflammation during perioperative period. One patient had adverse reaction with tocilizumab and switched to golimumab during perioperative period. The patients were treated with golimumab 50 mg every 4 weeks, along with concomitant treatment of glucocorticoid and immunosuppressants. After a median follow-up of (16.3±5.6) months, all the patients achieved clinical improvement. Vascular lesions were radiologically stable and no vascular progressive or newly-onset of vascular lesions was observed. The eight patients who experienced cardiac or vascular operations showed no evidence of postoperative complications. The ESR and hsCRP levels decreased significantly [16.5 (6.8, 52.5) mm/h vs. 4 (2, 7) mm/h, and 21.24 (0.93, 32.51) mg/L vs. 0.58 (0.37, 1.79) mg/L (P < 0.05), respectively]. The dose of prednisone was tapered from 35 (15, 60) mg/d to 10.0 (10.0, 12.5) mg/d. No prominent adverse reactions were observed. CONCLUSION Our study suggests that golimumab is effective in the treatment of severe/refractory cardiovascular BS. Combination immunosuppression therapy with golimumab contributes to control of inflammation, reduction of postoperative complications and tapering the dose of glucocorticoids or immunosuppressants.
Adult ; Antibodies, Monoclonal/therapeutic use* ; Behcet Syndrome/drug therapy* ; Drug Therapy, Combination ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome

Behcet syndrome (BS) is a chronic systemic inflammatory disorder involving vessels of all sizes, characterized by relapsing episodes of oral and/or genital ulcers, as well as skin lesions. Ocular, vascular, gastrointestinal, neurological system involvement can cause significant morbidity and mortality. Glucocorticoids and immunosuppressants are the cornerstones for the management of BS. Biologic agents has been recommended for severe and/or refractory BS. Interferon-α (IFN-α) had multiple biological effects, such as antiviral and antiproliferative, that could regulate both innate and adaptive immunity in BS. Growing evidence showed the efficacy of IFN-α in severe and/or refractory BS. Many studies have demonstrated that IFN-α has comparable effectiveness and tolerance profiles as anti-tumor necrosis factor (TNF) agents for Behcet's uveitis with a much lower cost and steroid-and immunosuppressant-sparing effects. IFN-α has been recommended as second-line therapy for ocular involvement of BS in EULAR (The European League Against Rheumatism) 2018. IFN-α also improves mucocutaneous lesions in BS with the dosage from 3 to 9-12 million IU three times per week. A few cases indicated the therapeutic potential of IFN-α in intestinal BS. As a new trial of IFN-α in vascular BS (VBS), a recent study revealed the lower relapse rate and higher recanalization rate with IFN-α in lower extremity deep vein thrombosis (DVT). Another two case reports presented the efficacy of IFN-α in pulmonary artery involvement in BS. Also, case reports have shown successful treatment in refractory neurological involvement. There are two subtypes of IFN-α commonly used in autoimmune diseases, named IFN-α2a and IFN-α2b. IFN-α2a seemed more effective than IFN-α2b, especially in ocular and mucocutaneous involvement of BS. Side effects of IFN-α are dose-dependent and not severe. The most frequent side effects are flu-like syndrome, mild leukopenia and alopecia. Considering the potential risk of tuberculosis (TB) and hepatitis B virus (HBV) reactivation of TNF-α inhibitors, IFN-α is safe due to its anti-HBV effect and protective effect on TB. In conclusion, IFN-α is a promising choice for severe and/or refractory BS patients, especially for those who are intolerant or contraindicant to other biological agents, such as TNF inhibitors. Further prospective controlled studies are warranted to confirm the efficacy and safety of IFN-α in BS.
Behcet Syndrome/drug therapy* ; Glucocorticoids ; Humans ; Immunosuppressive Agents ; Uveitis ; Venous Thrombosis

OBJECTIVE: Behcet's disease (BD) is an autoimmune disorder that causes most commonly mouth and genital ulcerations and erythema nodules of the skin and currently has limited options of therapeutic medicines. Metformin is recently reported to suppress immune reaction, and we hypothesized that metformin could be an option for treatment of BD. METHODS: Thirty patients with BD were enrolled in this perspective single-blinded, before-after study. We recorded the changes in the mucocutaneous activity index for BD (MAIBD), relapse frequency, C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) after metformin treatment to assess the changes in the disease activity. We also analyzed the changes in the protein and mRNA expression levels of Foxp3, interleukin-35 (IL-35), transforming growth factor-β (TGF-β), Ror-γt, IL-17, and tumor necrosis factor- (TNF-) in these patients using ELISA and qRT-PCR. RESULTS: Of the 30 patients enrolled, 26 completed the trial. After the treatment, favorable responses were achieved in 88.46% (23/26) of the patients, and partial remission was obtained in 11.54% (4/26) of them. During the treatment, 8 patients complained of gastrointestinal side effects, for which 4 chose to withdraw from the study in the first week. Our results showed that metformin treatment decreased MAIBD and relapse frequency in the patients, and significantly lowered the clinical inflammatory indexes including CRP and ESR. The results of ELISA and qRT-PCR revealed that metformin treatment obviously increased Foxp3 and TGF-β expressions at both the protein and mRNA levels and significantly decreased the levels of ROR-γt, IL-17 and TNF- as well as IL-35 level in these patients. CONCLUSIONS Metformin treatment relieves the clinical symptoms, reduces the inflammatory reaction indexes and regulates the Treg/Th17 axis in patients with BD, suggesting the potential of metformin as a candidate medicine for treatment of BD.
Behcet Syndrome ; drug therapy ; metabolism ; Controlled Before-After Studies ; Forkhead Transcription Factors ; metabolism ; Humans ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Interleukin-17 ; metabolism ; Interleukins ; metabolism ; Metformin ; adverse effects ; therapeutic use ; Neoplasm Recurrence, Local ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; metabolism ; RNA, Messenger ; metabolism ; Recurrence ; Single-Blind Method ; T-Lymphocytes, Regulatory ; cytology ; Th17 Cells ; cytology ; Transforming Growth Factor beta ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

No abstract available.
Aneurysm, Dissecting/diagnosis/*etiology/physiopathology/therapy ; Anticoagulants/therapeutic use ; Aortic Aneurysm/diagnosis/*etiology/physiopathology/therapy ; Behcet Syndrome/*complications/diagnosis/drug therapy ; Cerebral Infarction/diagnosis/etiology ; Diffusion Magnetic Resonance Imaging ; Echocardiography, Doppler, Color ; Electrocardiography ; Hemodynamics ; Humans ; Immunosuppressive Agents/therapeutic use ; Male ; Middle Aged ; *Sinus of Valsalva/physiopathology/ultrasonography ; Thrombosis/diagnosis/drug therapy/*etiology/physiopathology ; Ventricular Septal Rupture/diagnosis/*etiology/physiopathology/therapy

Behcet's disease (BD) involves multisystem vasculitis of unknown origin. Ocular manifestations of BD mostly include bilateral panuveitis and retinal vasculitis, which are very challenging to treat. Interferon alfa-2a (IFN) has been recently introduced for treating refractory Behcet uveitis, mainly in Germany and Turkey. Nonetheless, there is so far no consensus about the ideal treatment regimen of IFN for Behcet uveitis. We report our experience of IFN treatment in five Korean BD patients with refractory uveitis. All patients complained of oral ulcers; one patient had a positive pathergy test and 2 showed the presence of HLA-B51. Immunosuppressive agents used prior to IFN treatment included cyclosporine and methotrexate. The IFN treatment was commenced with a dose of 6-9 MIU/day for 7 days, adjusted according to individual ocular manifestations, tapered down to 3 MIU three times in a week, and then discontinued. All patients showed positive response to IFN treatment; 50% of them showed complete response without additional major ocular inflammation during the follow-up period. Other BD symptoms also improved after IFN treatment in most cases. After treatment, the relapse rate and the required dose of oral corticosteroid were decreased in most cases, showing a significant steroid-sparing effect. However, the visual acuity was not improved in most cases due to irreversible macular sequelae. Despite the small sample size of this study, we suggest that, in Korean patients, IFN is an effective treatment modality for BD uveitis as was observed in German and Turkish patients.
Adult ; Behcet Syndrome/complications/diagnosis/*drug therapy ; Chronic Disease ; Cyclosporine/therapeutic use ; Female ; Humans ; Immunosuppressive Agents/administration & dosage ; Interferon-alpha/*therapeutic use ; Male ; Recombinant Proteins/therapeutic use ; Recurrence ; Remission Induction ; Treatment Outcome ; Turkey ; Uveitis/diagnosis/*drug therapy/etiology ; Visual Acuity

BACKGROUND/AIMS: Anemia in patients with inflammatory bowel disease significantly affects the quality of life. The aim of this study was to investigate the frequency of and risk factors for anemia and to describe the management of anemia in patients with intestinal Behcet's disease (BD) in actual clinical practice. METHODS: We included 64 patients with intestinal BD who visited the outpatient clinic of a tertiary referral center in June 2011 and had available laboratory data for the subsequent 6 months. RESULTS: Anemia was detected in 26 patients (40.6%). After 6 months, anemia was still present in 14 of these patients (53.8%). The cause of anemia was investigated in eight patients (30.8%), and oral iron supplementation was prescribed to four patients (15.4%). Of these four patients, two (50%) recovered completely within 6 months. Anemia was associated with a high Disease Activity Index for Intestinal Behcet's Disease (DAIBD, p=0.024), erythrocyte sedimentation rate (p=0.003), and C-reactive protein (p=0.049) in univariate analysis. In multivariate analysis, the factor predictive for anemia in patients with intestinal BD was a higher DAIBD (> or =40; odds ratio, 4.08; 95% confidence interval, 1.21 to 13.71; p=0.023). CONCLUSIONS: Although anemia is common in intestinal BD patients, its clinical importance is overlooked in daily practice. Moderate to severe disease activity is predictive of anemia.
Adult ; Anemia/drug therapy/epidemiology/*etiology ; Behcet Syndrome/blood/*complications/pathology ; Blood Sedimentation ; C-Reactive Protein/analysis ; Dietary Supplements ; Disease Management ; Female ; Humans ; Intestinal Diseases/blood/*complications/pathology ; Iron/therapeutic use ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Predictive Value of Tests ; Risk Factors ; Severity of Illness Index ; Trace Elements/therapeutic use

No abstract available.
Behcet Syndrome/*complications/diagnosis/drug therapy ; Drug Therapy, Combination ; Hemianopsia/diagnosis/*etiology/physiopathology ; Humans ; Immunosuppressive Agents/administration & dosage ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Pulse Therapy, Drug ; Steroids/administration & dosage ; Treatment Outcome ; Visual Field Tests ; Visual Fields

PURPOSE: Behcet's disease (BD) is rarely reported to be associated with malignancies in the literature. However, the frequency of cancer in BD patients remains unknown. This study evaluated cancer morbidity in BD patients compared with that in the general population of Korea. MATERIALS AND METHODS: A retrospective chart review was performed on 506 patients visiting our hospital from 1994 to 2011 for BD. We analyzed the standardized morbidity rate (SMR), which is the ratio of observed to expected malignancies. Furthermore, we reviewed cases of solid cancer in BD patients in the literature. RESULTS: Of the 506 patients with BD, 11 (2.17%) developed cancer. We found a variety of solid cancers without predominance and no hematologic malignancies. The total number of cancers observed was less than expected, which was determined from the statistical data of the National Cancer Information Center of Korea, with an SMR of 0.023 (95% confidence interval, 0.012-0.039). CONCLUSION: BD may be associated with a lower cancer-related morbidity compared with the general population of Korea.
Adult ; Behcet Syndrome/*complications/drug therapy/epidemiology ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasms/*epidemiology/etiology/surgery ; Republic of Korea/epidemiology ; Retrospective Studies

Adult ; Behcet Syndrome ; complications ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Male ; Uveitis ; complications ; drug therapy

INTRODUCTIONThough oral aphthosis is common, it has a significant impact on the quality of life in the patients. It is the most common oral ulcerative condition encountered in clinical practice. This study describes the characteristics and patterns of oral aphthosis seen at a tertiary dermatological centre in Singapore, with emphasis in evaluating the management gaps and in identifying underlying systemic diseases and nutritional deficiencies.

MATERIALS AND METHODSThis is a retrospective review of medical records over a 10-year period between June 2000 and June 2010. Two hundred and thirteen patients were identified using the search terms 'oral ulcers', 'aphthous ulcers', 'oral aphthosis', and 'Behcet's disease'. Patients with Behcet's disease without oral ulcers and other diagnoses such as pemphigus vulgaris, lichen planus and herpes simplex were excluded. The remaining patients were evaluated with regard to demographic characteristics, characteristics of oral ulcers, associated connective tissue disorders and nutritional deficiencies, diagnostic tests results, treatment response as well as follow-up duration.

RESULTSOne hundred and seventy-fi ve patients were included in this study. One hundred and one patients had recurrent oral aphthosis, with 77 having simple aphthosis and 24 having complex aphthosis. Fourteen patients (8%) fulfilled the International Study Criteria (ISG) for Behcet's disease, of which, 85.71% had complex aphthosis. The therapeutic ladder for such patients ranged from topical steroids and colchicine through to oral corticosteroids and/or dapsone therapy.

CONCLUSIONRecurrent oral aphthosis is a niche condition in which dermatologists are well-poised to manage. This study demonstrates that a more definitive management and therapeutic algorithm for oral aphthosis are needed for better management patients in the future. In particular, complex aphthosis needs to be monitored for progression onto Behcet's disease.

Adolescent ; Adrenal Cortex Hormones ; therapeutic use ; Adult ; Aged ; Aged, 80 and over ; Anti-Infective Agents ; therapeutic use ; Anti-Inflammatory Agents ; therapeutic use ; Behcet Syndrome ; complications ; Child ; Child, Preschool ; Colchicine ; therapeutic use ; Dapsone ; therapeutic use ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Stomatitis, Aphthous ; diagnosis ; drug therapy ; etiology ; Treatment Outcome ; Tubulin Modulators ; therapeutic use ; Young Adult